CN114306723A

CN114306723A - Liquid embolic agent and preparation method and application thereof

Info

Publication number: CN114306723A
Application number: CN202111679662.2A
Authority: CN
Inventors: 张国艺; 郭远益; 虞鹏; 钱少君; 王亦群
Original assignee: Shenhong Medical Technology Shanghai Co ltd
Current assignee: Shenhong Medical Technology Shanghai Co ltd
Priority date: 2021-12-31
Filing date: 2021-12-31
Publication date: 2022-04-12

Abstract

The invention relates to a liquid embolic agent, a preparation method and application thereof. The liquid embolic agent comprises the following components in percentage by mass: 2 to 20 percent of polymer; 10% -40% of a developer, wherein the developer is porous particles containing developable metal; and 50-78% of solvent. The liquid embolic agent adopts the porous particles as the developer, so that the suspension stability of the developer in the liquid embolic agent is improved, the mixing time before use can be shortened, and the developing effect can be improved; in addition, the suspendable developer has a certain plasticizing effect on a polymer solution formed by the polymer and the solvent, and can interfere with entanglement among polymer molecules to a certain extent, so that the suspendable developer is beneficial to pushing of the liquid embolic agent.

Description

Liquid embolic agent and preparation method and application thereof

Technical Field

The invention relates to the technical field of medical instruments, in particular to a liquid embolic agent, a preparation method and application thereof.

Background

In the current clinical treatment of blood vessel abnormal focuses such as arteriovenous malformation (AVM) and arteriovenous fistula (DVF), the interventional embolization technology is an important treatment means.

Currently, there are two main categories of interventional embolization materials, solid and liquid. The solid embolization material is relatively simple in embolization process, but needs a large-diameter microcatheter, cannot enter a focal part close to AVM and the like for accurate embolization, and is easy to cause the problem of recanalization of blood vessels after particle embolization. Therefore, solid embolization materials are mostly used for preoperative embolization, and the requirement of curative embolization is difficult to meet. The liquid embolic agent has strong fluidity, can be uniformly filled in a diseased blood vessel after injection through a thinner micro catheter, realizes plugging after solidification, reduces the recanalization possibility of the blood vessel, and realizes precise and permanent embolism.

Among the liquid embolic agents, adhesive liquid embolic agents and non-adhesive liquid embolic agents are currently widely used clinically. Wherein the adhesive liquid embolic agent is mainly composed of cyanoacrylate. The non-adhesive liquid embolic agent is prepared by adding a developer into a DMSO solution of ethylene vinyl alcohol copolymer. Among the non-adhesive liquid embolizing agents, the most common is the Onyx liquid embolizing agent, which consists essentially of ethylene vinyl alcohol copolymer, dimethyl sulfoxide, and micron-sized tantalum powder as developers. The embolization principle of the Onyx liquid embolization agent is that metal tantalum powder is vigorously stirred or vibrated for a long time in dimethyl sulfoxide solution with micron-sized tantalum powder as a developer polymer to form tantalum powder suspension, and the suspension is injected into blood vessels of focuses such as intracranial and the like through a micro catheter to form embolization masses to block blood vessel passages, so that the aim of blocking blood flow is fulfilled.

These liquid embolizing agents use as imaging agents a solvent-insoluble metal powder, such as metallic tantalum powder, tantalum being a group VB element, having an atomic number of 73, and have good radiopacity and a density of 16.65g/cm³Insoluble in water and most solvents, therefore, tantalum powder is used as a developer for liquid embolic agents which are easy to standSedimentation of the developer occurs. Therefore, the precipitation of tantalum powder may occur during the pushing process, resulting in that part of the embolization agent cannot be dispersed to deeper diseased parts, and the precipitation of part of the developer causes the concentration of the developer to change, resulting in the loss of developing performance.

Disclosure of Invention

Therefore, a liquid embolic agent with better developing performance, a preparation method and application thereof are needed.

The invention is realized by the following technical scheme.

In one aspect of the present invention, there is provided a liquid embolic agent, comprising by mass:

2 to 20 percent of polymer;

10% -40% of a developer, wherein the developer is porous particles containing developable metal; and

50 to 78 percent of solvent.

In some of these embodiments, the liquid embolic agent further comprises a therapeutic agent at a concentration of 0.1-50 mg/mL.

In some of these embodiments, the therapeutic agent is at least one of a vascular proliferation inhibitor and a vasospasm therapeutic agent.

In some of these embodiments, the angiogenesis inhibitor comprises at least one of sorafenib, vandetanib, regorafenib, aflibercept, combaiccept, paclitaxel, and a paclitaxel derivative;

the vasospasm therapeutic agent comprises at least one of nimodipine and fasudil.

In some of these embodiments, at least a portion of the therapeutic agent is loaded on the imaging agent to form drug-loaded particles.

In some of these embodiments, the developable metal is at least one of gold, silver, platinum, iridium, chromium, tantalum, bismuth, cobalt, tungsten, and barium.

In some embodiments, the porous particles are made of a metal or an alloy of the developable metal;

alternatively, the material of the porous particles is a metal compound formed of the developable metal.

In some of these embodiments, the metal compound is at least one of a metal salt, a metal oxide, a metal carbide, and a metal nitride formed from the developable metal that is insoluble in the solvent.

In some of these embodiments, the porous particles are hollow particles, the surface of the hollow particles being porous;

or, the porous particles are solid particles, and the interior and/or the surface of the solid particles are provided with porous holes.

In some embodiments, the liquid embolic agent comprises, by mass percent, 3% to 10% of the polymer, 20% to 40% of the imaging agent, 0.2% to 2% of the therapeutic agent, and 60% to 75% of the solvent.

In some of these embodiments, the polymer is any one of a polyolefin, a polyolefinic alcohol, a polymethacrylate, a polyurethane, a polyester, a polyether, a polysiloxane, and a polyamide, or a copolymer of at least two thereof;

and/or the solvent is at least one of a biocompatible organic solvent, water and a buffer solution.

In another aspect of the present invention, there is provided a method for preparing a liquid embolic agent, comprising the steps of:

mixing the components of the liquid embolic agent uniformly.

In some of these embodiments, the method of making further comprises: a step of preparing the developer by a polymer templating method, a method of calcination or hydrocracking.

In some of these embodiments, the polymer templating method comprises: and forming a metal layer, an alloy layer or a metal compound layer on the surface of the polymer microsphere by taking the polymer microsphere as a template, and removing the core polymer microsphere template to obtain the hollow microsphere made of a metal material, an alloy material or a metal compound material.

In another aspect of the present invention, there is provided a use of the liquid embolic agent of any of the above in the preparation of a medical interventional device or an interventional treatment drug.

In another aspect of the present invention, there is provided a medical intervention device comprising a device body and a reagent provided in the device body, wherein the reagent contains the liquid embolic agent according to any of the above aspects.

In another aspect of the invention, there is provided an interventional procedure comprising a liquid embolic agent as defined in any of the above.

The liquid embolic agent adopts porous particles containing developable metal as the developer, and compared with the traditional micron-sized tantalum powder with a non-porous structure, the liquid embolic agent improves the suspension stability of the developer in the liquid embolic agent, thereby not only shortening the mixing time before use, but also improving the development effect; in addition, the suspendable developer has a certain plasticizing effect on a polymer solution formed by the polymer and the solvent, and can interfere with entanglement among polymer molecules to a certain extent, so that the suspendable developer is beneficial to pushing of the liquid embolic agent.

Furthermore, the liquid embolic agent can also contain a therapeutic agent with a specific proportion, and the therapeutic agent can have therapeutic effect on other disease symptoms possibly appearing around the diseased blood vessel, so that the therapeutic effect on other disease symptoms can be effectively improved along with the liquid embolic agent in the interventional therapy process or when the curative embolism is realized.

Drawings

FIG. 1 is a schematic view of the state of the art liquid embolic agent;

FIG. 2 is a schematic view of the state of a liquid embolic agent according to an embodiment of the present invention;

fig. 3 is a schematic view of the state of a liquid embolic agent according to another embodiment of the present invention.

Description of reference numerals:

11. a polymer; 12. a developer; 121. a hole; 13. a therapeutic agent.

Detailed Description

In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. It is to be understood that these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless specifically limited otherwise.

The invention provides a liquid embolic agent, which comprises the following components in percentage by mass: 2-20% of polymer, 10-40% of developer and 50-78% of solvent.

Wherein the developer is porous particles containing a developable metal.

In some of these embodiments, the liquid embolic agent further comprises a therapeutic agent at a concentration of 0.1-50 mg/mL. Although interventional embolization techniques can achieve curative embolization and prevent recanalization of blood flow, it has been found that other disease conditions, such as vascular hyperplasia, may occur around the diseased vessel during interventional procedures or during clinical follow-up. The liquid embolic agent also contains a therapeutic agent with a specific proportion, and the liquid embolic agent can have therapeutic effect on other disease symptoms possibly appearing around a diseased blood vessel, so that the therapeutic effect on other disease symptoms can be effectively improved along with the liquid embolic agent in the interventional therapy process or when curative embolism is realized.

In some of these embodiments, the therapeutic agent is at least one of a vascular proliferation inhibitor and a vasospasm therapeutic agent. For example, in one example, the therapeutic agent is a blood vessel proliferation inhibitor, and the concentration of the blood vessel proliferation inhibitor in the liquid embolic agent is 0.1-50 mg/mL by mass, and preferably 0.2-20 mg/mL by mass.

The angiogenesis inhibitor can be approved drugs for inhibiting angiogenesis, and further comprises at least one of sorafenib, vandetanib, regorafenib, aflibercept, combaicipu, paclitaxel and derivatives thereof.

Wherein the vasospasm therapeutic agent is administered locally and rapidly for inducing immediate vasospasm treatment during surgery. Further, the vasospasm therapeutic agent includes at least one of nimodipine and fasudil.

In some of these embodiments, the solvent is at least one of a biocompatible organic solvent, water, and a buffer. Further, the biocompatible organic solvent includes at least one of dimethyl sulfoxide, N-methylpyrrolidone (NMP), ethanol, and isopropanol, and these biocompatible solvents have low toxicity. It is understood that the solvent may be selected according to the kind of the polymer, as long as it enables the polymer and the solvent to form a homogeneous system. Homogeneous system here means a homogeneous clear solution or a homogeneous suspension. Further, the solvent may be a good solvent for the above-mentioned polymer, i.e., the solvent and the polymer can form a uniform clear solution, or the solvent and the polymer can form a uniform system under specific conditions.

The developable metal is a metal that is visible under X-rays. In some of these embodiments, the developable metal is at least one of gold (Au), silver (Ag), platinum (Pt), iridium (Ir), chromium (Cr), tantalum (Ta), bismuth (Bi), cobalt (Co), tungsten (W), and barium (Ba). In some embodiments, the developable metal can also include at least one of a lanthanide, an actinide metal.

Further, the material of the porous particles is a metal or an alloy of the developable metal. The alloy can be a metal alloy formed by the two developable metals.

Further, the material of the porous particles is a metal compound formed of a developable metal.

Further, the metal compound is at least one of a metal salt, a metal oxide, a metal carbide, and a metal nitride formed of one of the developable metals and insoluble in the solvent. For example, the metal compound material may be silver halide, bismuth oxide, tantalum carbide, barium sulfate, tantalum nitride, tungsten oxide, tantalum oxide, or the like.

Further, the metal salt, the metal oxide, the metal carbide and the metal nitride are compounds which are not water-soluble and are not soluble in an organic solvent.

It is understood that the developer may be at least one of porous particles of a metal or alloy material and porous particles of a metal compound material, or a combination of porous materials.

In some of these embodiments, the porous particles have a porosity of 10% to 70%, preferably 20% to 50%. Wherein, the porosity is the percentage of the pore volume in the porous particles to the total volume of the material in the natural state.

In some of these embodiments, the porous particles are hollow particles or solid particles.

Further, the porous particles are hollow particles, and the surfaces of the hollow particles are porous.

For hollow particles, the wall thickness of the hollow particles and the particle size of the microspheres can be optimized to obtain a proper average density, and the average density can ensure that the hollow particles have better suspension property in the liquid embolic agent, are easy to disperse and are not easy to settle. In some examples, the particle size of the hollow particles made of the metal compound material is in a range of 0.1 to 200 μm, preferably 0.5 to 50 μm. In some examples, the hollow particles of metal material have a wall thickness in the range of 20nm to 20 μm.

Further, the morphology of the porous particles is microspheres, for example, hollow microspheres. The hollow microspheres can be prepared by a polymer template method. The polymer template method is that polymer microspheres are used as templates, a metal layer, an alloy layer or a metal compound layer is formed on the surfaces of the polymer microspheres, and then the polymer microsphere templates are removed.

For example, the hollow microspheres are prepared as follows: firstly preparing polymer microspheres with a certain particle size by adopting methods such as emulsion polymerization or self-assembly and the like, and then depositing or modifying a metal compound on the surfaces of the polymer microspheres to form a metal layer, an alloy layer or a metal compound layer. And then eluting by using a specific solvent to remove the polymer microsphere body serving as the inner core, or removing the polymer microsphere body by calcining or other means at a specific temperature to obtain the hollow metal compound material microsphere. The hollow microspheres can also be obtained by using a solvent and calcining simultaneously, for example, eluting with the solvent and then removing the polymer microsphere body by calcining. The polymer microspheres used therein can be obtained by direct commercial purchase, for example, polyethylene, polystyrene-divinylbenzene, etc. Wherein, the shell layer can form holes by controlling the molecular growth and accumulation process of the shell layer.

Further, the porous particles are solid particles having porous pores, which may be distributed internally and/or on the surface, which are not or partially open.

Further, the porous particles are microspheres, that is, the porous particles are solid microspheres.

In some examples, the solid microspheres are prepared by the above-mentioned method for preparing hollow microspheres, except that the steps of eluting with a solvent and calcining to remove the polymer microsphere body are not performed, so that the microspheres with a core-shell structure with the polymer microspheres as the inner core and the metal layer, the alloy layer or the metal compound layer as the outer shell are obtained. Wherein, the shell layer can form holes by controlling the molecular growth and accumulation process of the shell layer.

In other examples, porous solid particles may also be prepared by calcination or hydrocracking. The calcination is to add a space occupying agent or a pore forming agent to sinter and melt particles made of materials such as metal, alloy, metal compound and the like, and then remove the space occupying agent or the pore forming agent to obtain the catalyst. The hydrogen breaking is to introduce hydrogen in the preparation process, control the hydrogen absorption amount of the particles of materials such as metal, alloy, metal compound and the like, then break and remove hydrogen to form porous holes.

It is understood that the developer may contain only hollow particles, or only solid particles, or both hollow and solid particles.

As shown in fig. 1, the conventional liquid embolic agent can adopt metal or metal compound powder as a developing material, and the polymer 11, the developing agent 12 and the therapeutic agent 13 are simply mixed with each other in a solvent, wherein the developing agent 12 is solid metal or metal compound powder.

In some embodiments, referring to fig. 2, the polymer 11, the imaging agent 12, and the therapeutic agent 13 are mixed in a solvent, wherein the imaging agent 12 is porous particles containing a developable metal, and the porous imaging agent 12 can be hollow particles, solid particles, or a mixture of hollow and solid particles, as described above. In this embodiment, at least a portion of the polymer 13 may be interpenetrated within the pores and/or hollow of the porous developer 12. In addition, the suspended porous developer 12 has a certain plasticity in the mixed solution of the polymer 11, and in conclusion, the existence of the porous developer 12 interferes with the entanglement of the molecules of the polymer 11, and is beneficial to pushing the liquid embolic agent in the microcatheter.

Referring to fig. 3, in other embodiments, at least a portion of the therapeutic agent 13 can be supported on the imaging agent 12 to form drug-loaded particles. The polymer 11 and the drug-loaded particles are mixed with each other in the solvent, and the polymer 11 and the drug-loaded particles are in a mixed state in the liquid embolic agent. At this time, the developer 12 serves both as a developing agent and a drug carrier. The porous particles facilitate loading of the therapeutic agent, which may facilitate stabilization of the loading of both. The therapeutic agent, especially the angiogenesis inhibitor therapeutic agent, is loaded on the developing agent to form the drug-loaded particles, so that the risk that the therapeutic agent is carried away by the solvent along with the diffusion of the solvent can be reduced, and meanwhile, after the liquid embolic agent is solidified, the therapeutic agent of the drug-loaded particles can be slowly released, thereby playing the role of prolonging the drug effect. Therefore, the therapeutic agent is loaded on the developing agent, so that the use of other drug carriers is omitted, the probability of the therapeutic agent reaching the focus can be improved, and the therapeutic effect of the therapeutic agent in the focus area can be effectively exerted.

In the specific example shown in fig. 3, a part of the therapeutic agent 13 is supported on the porous particle-carrying developer 12 to form drug-carrying particles, and the other part of the therapeutic agent 13 and the solvent are in a state of being mixed with each other, and further, there may be a part of the developer 12 not supporting the therapeutic agent. Further, of the drug-loaded particles, the therapeutic agent 13 is preferably loaded in the pores 121 of the developing agent 12. In embodiments of the hollow porous particle imaging agent 12, the therapeutic agent 13 may also be supported in the hollow of the imaging agent 12.

Preferably, the angiogenesis inhibitor is loaded in the developer to form drug-loaded particles, and then the drug-loaded particles are mixed with other components such as polymer, solvent and the like to form the liquid embolic agent. The liquid embolic agent is adopted to realize curative embolism around a diseased blood vessel and prevent blood flow from recanalizing, and meanwhile, the drug-loaded particles loaded with the angiogenesis inhibitor can slowly release the angiogenesis inhibitor therein, so that the angiogenesis inhibitor can be promoted to exert drug effect around the diseased blood vessel for a long time, the risk of angiogenesis is reduced, and the success rate of curative embolism is increased.

Still further, in other examples, the therapeutic agent 13 is loaded on the imaging agent to form drug-loaded particles.

It will be appreciated that in some embodiments, in conjunction with the embodiments of fig. 2 and 3, at least a portion of the polymer 11 and at least a portion of the therapeutic agent 13 may be interspersed or carried within the imaging agent 12, providing the multiple advantages described above and not described in further detail herein.

Further preferably, in the liquid embolic agent, the polymer is 3-10%, the developer is 20-40%, and the solvent is 60-75% by weight.

In some of these embodiments, the polymer is any one of a polyolefin, a polyolefinic alcohol, a polymethacrylate, a polyurethane, a polyester, a polyether, a polysiloxane, and a polyamide, or a copolymer of at least two thereof. Further, the copolymer can be polyacrylamide-polymethyl methacrylate, ethylene-vinyl alcohol copolymer, polyethylene glycol-polyacrylate copolymer, and the like, and can also be a natural polymer which is difficult to dissolve in water, such as cellulose and derivatives thereof, and the like. Further, copolymers include, but are not limited to, atactic copolymers, block copolymers, alternating copolymers, and graft copolymers.

Further, the weight average molecular weight of the polymer is 1 to 40 ten thousand, preferably 10 to 25 ten thousand. Further, the molar content of the hydrophobic component of the polymer is more than 35%, preferably more than 45%. Wherein the hydrophilic component is a hydrophilic group contained in a side chain or a main chain of the polymer, and is a hydrophobic component otherwise. The higher the content of the hydrophobic component, the shorter the time for the polymer to be precipitated in water, buffer solution or blood, and the lower the solidification rate, and the solidification rate of the liquid embolic agent can be controlled by adjusting the proportion of the hydrophilic and hydrophobic components.

The invention also provides a preparation method of the liquid embolic agent, which is to mix the polymer, the solvent and other components uniformly.

Further, the mixing may be carried out by a conventional method such as stirring or ultrasonic, as long as the liquid embolic agent can be formed into a uniform system.

Further, the polymer and the solvent can be mixed by mechanical stirring and the like to form a polymer solution with a uniform phase, then the developer is added, and the polymer solution and the solvent are mixed by mechanical stirring and the like to form a uniform dispersion system.

Furthermore, in the step of forming a homogeneous phase polymer solution, the dissolution can be assisted by heating, cooling, physical dispersion, and the like.

When the liquid embolic agent forms a uniform dispersion system, a conveying or pushing mode can be adopted, after the liquid embolic agent reaches water or blood, polymers in the liquid embolic agent precipitate out along with the diffusion of a solvent to form a soft embolic group, and a developer in the embolic group ensures good developing performance of the soft embolic group.

The invention also provides the application of the liquid embolic agent in the preparation of medical interventional instruments or interventional treatment medicines.

Another embodiment of the present invention further provides a medical interventional device, a device body and a reagent disposed in the device body, the reagent comprising a liquid embolic agent as defined in any of the above.

In some of these embodiments, the instrument body is a catheter. Further, the inner diameter of the catheter is small, and is called a microcatheter. Typically, the microcatheter has an inner diameter of 0.007 to 0.013 inch.

In another embodiment, the present invention provides an interventional procedure comprising a liquid embolic agent according to any of the above.

Further, the interventional therapy medicament may contain other additives in addition to the liquid embolic agent as in any of the above.

The liquid embolic agent can be used in interventional therapy, such as in interventional hemostasis, vascular malformations and malignant tumors, including but not limited to interventional embolization of cerebral arteriovenous malformations (AVM), hematomas, and cerebral arteriovenous fistulas (DVF), peripheral blood vessel varices, and occlusion of blood flow at tumors.

The liquid embolic agent reaches the focal region through the bolus injection of the microcatheter, contacts the blood stream, and begins to solidify as the solvent is dispersed. In the blood flow, the polymer in the liquid embolic agent is slowly precipitated, separated and solidified to form an embolic mass, thereby achieving the purposes of plugging the vascular access and blocking the blood flow; meanwhile, the therapeutic agent can effectively improve the treatment effect on other disease symptoms in the interventional therapy process or in the process of realizing curative embolism. In some embodiments, the liquid embolic agent comprising the developable porous metal particles has a lower average bulk density and lower viscosity, and the microcatheter can be easily withdrawn after the liquid embolic agent is completely pushed out of the microcatheter, reducing the risk of the microcatheter being pulled on the blood vessel.

In order to make the objects, technical solutions and advantages of the present invention more concise and clear, the present invention is described with the following specific embodiments, but the present invention is by no means limited to these embodiments. The following described examples are only preferred embodiments of the present invention, which can be used to describe the present invention and should not be construed as limiting the scope of the present invention. It should be understood that any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

In order to better illustrate the invention, the following examples are given to further illustrate the invention. The following are specific examples.

Example 1

The preparation method of the liquid embolic agent containing the tantalum hollow microspheres comprises the following steps:

adding 5g of polymer polyhydroxyethyl methacrylate into 60g of dimethyl sulfoxide, stirring for 2h at room temperature, adding 20g of tantalum hollow microspheres, and mixing for 10min at room temperature by using a shaking mixer to obtain uniform suspension, namely the liquid embolic agent.

The liquid embolic agent is a suspension and has good propelling performance through a syringe or a micro-catheter. The solidified embolus has good visibility under X-ray.

Example 2

Preparation of liquid embolization microspheres comprising tantalum oxide hollow microspheres and angiogenesis inhibitor:

(1) adding 2g of ethylene vinyl alcohol copolymer into 15g of dimethyl sulfoxide, stirring and dissolving at 60 ℃, and cooling to room temperature to form an ethylene vinyl alcohol polymer solution.

(2) Adding 0.1g of angiogenesis inhibitor taxol into 5g of dimethyl sulfoxide, stirring and dissolving at room temperature, adding 5g of tantalum oxide hollow microspheres, and continuously stirring for 1h to form a drug-loaded microsphere solution.

(3) And (3) mixing the ethylene vinyl alcohol polymer solution obtained in the step (1) with the drug-loaded microsphere solution obtained in the step (2), and shaking and mixing at normal temperature for 20min to obtain a uniform suspension, namely a liquid embolic agent.

Comparative example 1

As shown in FIG. 1, comparative example 1 is a prior art liquid embolic agent prepared by using solid tantalum oxide powder as a developer, and the polymer and the solvent are not limited.

The liquid embolization agent of comparative example 1, which used tantalum oxide of non-porous structure without solid powder as the developer, had poor suspension stability in the liquid embolization agent and long mixing time before use; the metal density is high, certain sedimentation exists in the pushing process in an injector or a micro-catheter, and the pushing of the liquid embolic agent is not facilitated; the solid tantalum oxide powder developer and the therapeutic agent are simply mixed in the solvent, and the developer does not have the functions of a drug carrier and drug slow release; the development effect of the plug mass formed after curing under X-ray is clearly less clear than in example 1.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the patent of the invention is subject to the appended claims, and the description can be used for explaining the contents of the claims.

Claims

1. The liquid embolic agent is characterized by comprising the following components in percentage by mass:

2 to 20 percent of polymer;

50 to 78 percent of solvent.

2. The liquid embolic agent of claim 1, further comprising a therapeutic agent at a concentration of 0.1 to 50 mg/mL.

3. The liquid embolic agent of claim 2, wherein said therapeutic agent is at least one of a vascular proliferation inhibitor and a vasospasm therapeutic agent.

4. The liquid embolic agent of claim 3, wherein the angiogenesis inhibitor comprises at least one of sorafenib, vandetanib, regorafenib, aflibercept, combaiccept, paclitaxel, and a paclitaxel derivative;

and/or, the vasospasm therapeutic agent comprises at least one of nimodipine and fasudil.

5. The liquid embolic agent of claim 2, wherein at least a portion of said therapeutic agent is loaded on said imaging agent to form drug-loaded particles.

6. The liquid embolic agent of any of claims 1 to 5, wherein said developable metal is at least one of gold, silver, platinum, iridium, chromium, tantalum, bismuth, cobalt, tungsten, and barium.

7. A liquid embolic agent according to any of claims 1 to 5, wherein said porous particles are of a metal or alloy of said developable metal;

8. The liquid embolic agent of claim 7, wherein said metal compound is at least one of a metal salt, a metal oxide, a metal carbide, and a metal nitride formed of said developable metal that is insoluble in said solvent.

9. The liquid embolic agent of any of claims 1 to 5, 8, wherein said porous particles are hollow particles, the surface of said hollow particles being porous;

10. The liquid embolic agent of any of claims 1 to 5, 8, wherein said polymer is any one of a polyolefin, a polyolefinic alcohol, a polymethacrylate, a polyurethane, a polyester, a polyether, a polysiloxane, and a polyamide, or a copolymer of at least two thereof;

11. A method for preparing a liquid embolic agent, comprising the steps of:

mixing the components of the liquid embolic agent of any of claims 1 to 10 uniformly.

12. The method of claim 11, further comprising: a step of preparing the developer by a polymer templating method, a method of calcination or hydrocracking.

13. The method of claim 12, wherein the polymer templating process comprises: and forming a metal layer, an alloy layer or a metal compound layer on the surface of the polymer microsphere by taking the polymer microsphere as a template, and removing the core polymer microsphere template to obtain the hollow microsphere made of a metal material, an alloy material or a metal compound material.

14. Use of a liquid embolic agent according to any of claims 1 to 10 for the manufacture of a medical interventional device or an interventional treatment drug.

15. A medical intervention device comprising a device body and an agent disposed within the device body, the agent comprising a liquid embolic agent according to any of claims 1 to 10.

16. An interventional procedure comprising a liquid embolic agent according to any of claims 1 to 10.